This invention relates to a novel process for preparing the well known herbicide 2-amino-4-(hydroxymethylphosphinyl)butanoic acid, as well as other biologically active compounds, and to certain compounds useful as intermediates in the process.
The compound L-2-amino-4-(hydroxymethylphosphinyl)butanoic acid, also known in the art as phosphinothricin or glufosinate, is an effective broad spectrum phytotoxicant useful in controlling the growth of emerging seedlings and maturing and established woody and herbaceous vegetation. The compound can be represented by the formula: ##STR1##
Phosphinothricin, where R is methyl, is a naturally occurring phosphinic acid analog of L-glutamate. Its activity has been attributed to an ability to inactivate the enzyme glutamine synthetase, thus blocking in vivo ammonia incorporation into amino acids and pyrimidines. Phosphinothricin was first isolated from two different streptomycete species, although the racemic P-ethyl analog was prepared considerably earlier and was shown to inhibit glutamine synthetase.
Rupp et al, U.S. Pat. No. 4,168,963, refer to earlier described methods for the preparation of phosphinothricin, which include base-catalyzed reactions of dialkyl acetamidomalonate esters with alkyl 2-haloethylmethylphosphinate esters or alkyl methylvinylphosphinate esters, as well as Strecker synthesis on 3-(alkoxymethylphosphinyl)propanoic aldehydes.
Minowa et al, U.S. Pat. No. 4,510,102, refer to other earlier described methods for the preparation of phosphinothricin, including the Michaelis-Arbuzov reaction of diethyl methylphosphonite with methyl 4-bromo-2-trifluoroacetamidobutanoate, a method characterized by low yields and instability of the brominated intermediate. Minowa et al further disclose a new preparation of phosphinothricin which involves the coupling of vinyl magnesium halides with alkyl methylphosphinyl halides, followed by base-catalyzed addition to the resulting alkyl methylvinylphosphinates of certain Schiff bases of alkyl glycinates, and subsequent hydrolysis.
Minowa et al, U.S. Pat. No. 4,499,027, disclose a new preparation of optically pure isomers of phosphinothricin which involves the base-catalyzed addition to alkyl methylvinylphosphinates of certain Schiff bases prepared from alkyl glycinates and optically active 2-hydroxypinan-3-ones.
Although these and other methods are available for the preparation of phosphinothricin, they are characterized by the use of strong bases and/or harsh conditions which are necessary to achieve the final end product. Thus, there still remains a need for processes to prepare phosphinothricin, its P-ethyl analog, and other phosphinylbutanoic acids, which produce the desired products in high yields and without the use of strong base or harsh conditions.